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Cartilage Mechanobiology
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Hai Yao, Yongren Wu, Xin L. Lu
Mechanical loading can cause robust fluctuation of intracellular calcium concentration by activating PLC and IP3 pathway [172,194] through IL-4 [183]. As one of the earliest intracellular responses in chondrocytes under mechanical stimulation, calcium signaling can initiate or regulate the secretion of growth factors and cytokines. The released autocrine or paracrine factors may bind to transmembrane receptors, such as G-protein coupled receptors (GPCR), to further initiate MAPK, PKC, and NF-kB pathways. Additionally, it can activate calmodulin kinase, resulting in the activation of transcription factor AP-1. It has been shown that aggrecan gene expression and electrophysiological response were suppressed under cyclic loading (0.33 Hz, 20 min) when the calmodulin pathway was inhibited [172]. Cyclic AMP (cAMP), another important second messenger for PG synthesis, can also cross-talk with calcium signaling [119]. It has been shown that gene expressions of bovine cartilage explants were regulated by cAMP through PKA pathway under static compression [95].
Cellular Stress Responses Following Photodynamic Therapy
Published in Barbara W. Henderson, Thomas J. Dougherty, Photodynamic Therapy, 2020
Stefan W. Ryter, Charles J. Gomer, Angela Ferrario, Anita M. R. Fisher, Marian Luna, Natalie Rucker, Sam Wong
The AP-1 sequence element, also called the TRE or 12′-O-tetradecanoyl-phorbol-13-acetate (phorbol ester) responsive element, functions as a binding site for transcription factor AP-1, which is a heterodimeric complex of the protooncogene products c-FOS and c-JUN [30]. The AP-1 element mediates transcriptional induction following the stimulation of signal transduction pathways involving the phorbol ester or diacylglycerol-dependent activation of protein kinase C [30]. Potential AP-1–binding sites exist within promoters of several oxidative stress-PDT-inducible genes, including metallothionein [31] and heme oxygenase [32]. The serum responsive element (SRE) or CArG box, renders the c-fos promoter inducible by serum stimulation or subject to feedback inhibition by c-FOS [33,34]. The c-fos mRNA accumulation has been observed as an immediate response to PII-mediated PDT in RIF-1 cells, with a maximum occurring approximately 30 min after light treatment. Porphyrin incubation conditions also induce c-fos. Transcriptional activation of c-fos, in combination with the activation of protein kinase C-dependant phosphorylation may be an early event in a cascade culminating in the transcription of genes with AP-1 sequence elements [35]. The AP-1-binding transcription factors could play a role in the transactivation of stress protein promoters following oxidative stress. Studies designed to evaluate AP-1 transcription factors must control for cell culture manipulations since the c-fos promoter has a serum responsive element (SRE) and responds to fluctuations in medium serum content. The rat heme oxygenase promoter also contains other 5′ eis elements that mediate transactivation under different stress conditions, including a heat shock consensus sequence (HSE) and a metal responsive element (MRE)[32].
Herbs in Cancer Therapy
Published in Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam, Herbal Product Development, 2020
Annum Malik, Shahzadi Sidra Saleem, Kifayat Ullah Shah, Learn-Han Lee, Bey Hing Goh, Tahir Mehmood Khan
In new clinical procedures, emphasis is laid on the blocking of specific cell signaling transduction pathways involved in converting normal cells into cancerous cells. Herbal drugs play their anticancerous role by blocking some of these pathways as follows: Pathway involving the activation of activator protein-1 (AP-1) and NF-kB: Pathogenesis of various inflammatory diseases including cancer, diabetes, rheumatoid arthritis, and atherosclerosis depends upon the activation of the NF-kB activation pathway.NF-kB along with other transcription factors including AP-1 regulates genes which play their role in angiogenesis and aggressive growth leading to cancer (Hemalswarya and Doble 2006). Mountain ginseng extract has shown to inhibit the lungs cancer cell growth through attenuating cancerous cells proliferation and by inducing apoptosis which is resulted through the controlling of NF-kB signaling transduction pathway (Hwang et al. 2012).Signal transduction through PTK: Polypeptide growth factors includes platelet derived growth factor (PGDF). These binds to their specific receptors which are called tyrosine kinesis. This binding of peptide growth factors with their receptors results in increased signal transduction to cancerous cells. Overexpression has been reported of these growth factors and their associated tyrosine kinesis receptors (Hemalswarya and Doble 2006).MAPK pathway: Activation of mitogen activated protein kinase (MAPK) cause proliferation of the cells. Variety of tumors are owing to the dysregulation in this MAPK pathway. Therefore an effective chemotherapy involves targeting of this MAPK pathway (Hemalswarya and Doble 2006). Zengshenping (zsp) is applied because it increases Capase-3 expression thus inducing tumor cell apoptosis (Guan et al. 2012).Cyclooxygenase-2 (COX-2) pathway: Proliferation as well as angio-genesis, either can be inhibited or stopped by the inhibition of cyclooxygenase (COX), mainly COX-2. This inhibition results in termination of the prostaglandin (PG) cascade ultimately effecting the growth of cancerous cells (Cragg and Newman 2005).
Inhibitory effect of particulate matter on toll-like receptor 9 stimulated dendritic cells by downregulating mitogen-activated protein kinase and NF-κB pathway
Published in Journal of Toxicology and Environmental Health, Part A, 2020
Madeeha Arooj, Irshad Ali, Hee Kyoung Kang, Jin Won Hyun, Young-Sang Koh
MAPKs activation upregulates AP-1 transcription factor, which leads to induction of AP-1 dependent genes including cytokines (Akira and Takeda 2004; Blasius and Beutler 2010; Huang and Yang 2010). To investigate, the influence of PM2.5 on AP-1 transcriptional activity, luciferase assay was performed on HEK293 T cells transfected with empty pcDNA3 or pcDNA3-mTLR9. HEK293 T cells transfected with empty pcDNA3 showed no induction of AP-1 dependent luciferase activity upon CpG-DNA stimulation. However, pcDNA3-mTLR9 exhibited a rise in AP-1 dependent luciferase activity. In contrast, PM2.5 treatment induced marked concentration-dependent inhibition on AP-1 dependent luciferase activity in HEK293 T cells transfected with pcDNA3-mTLR9 (Figure 5a).
Ozone ultrafine bubble water induces the cellular signaling involved in oxidative stress responses in human periodontal ligament fibroblasts
Published in Science and Technology of Advanced Materials, 2019
Anongwee Leewananthawet, Shinichi Arakawa, Tokuju Okano, Ryo Daitoku Kinoshita, Hiroshi Ashida, Yuichi Izumi, Toshihiko Suzuki
AP-1, a family of dimeric transcription factors, including c-Jun and c-Fos, activates the transcription of downstream gene expressions by translocating from the cytoplasm to the nuclei upon stimulation by oxidative stress. Since the p38 MAPK signaling cascade is involved in AP-1 activation by H2O2 [14], we examined the localization of c-Fos after treatment with OUFBW. The strong fluorescence signal of c-Fos in the nuclei was detected in the cells treated with OUFBW as well as PMA, but not in those exposed to inactive OUFBW (Figure 4(a)). Quantified analysis of the nuclear localization of c-Fos supported the results (Figure 4(c)), suggesting the activation of c-Fos by the ozone in OUFBW. The Nrf2-mediated pathway is the major regulator of cytoprotective responses to oxidative stress [16]. Also, activation of MAPK pathways induces antioxidant response element (ARE)-mediated gene expression via an Nrf2-dependent mechanism [17]. Oxidative stress stabilizes Nrf2 by preventing association with inhibitor protein Keap1, followed by translocation of Nrf2 into the nuclei [16]. Therefore, we next examined the cellular location of Nrf2 after treatment with OUFBW. Similar to the case of c-Fos, Nrf2 was translocated into the nuclei of the cells treated with OUFBW (Figure 4(b,d)). Taken together, these data suggest that the ozone in OUFBW stimulates cell signaling via c-Fos or Nrf2 in the hPDLFs.